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DUET-1: Week-48 Results of a Phase III Randomized Double-blind Trial to Evaluate the Efficacy and Safety of TMC125 vs Placebo in 612 Treatment-experienced HIV-1-infected Patients
Richard Haubrich*1, P Cahn2, B Grinsztejn3, J Lalezari4, J Madruga5, A Mills6, M Peeters7, J Vingerhoets7, K Iveson8, G De Smedt7, and on behalf of the DUET-1 study group
1Univ of California, San Diego, US; 2Hosp Juan A Fernandez and Fndn Huesped, Buenos Aires, Argentina; 3Inst de Pesquisa Clinica Evandro Chagas, FIOCRUZ, Brazil; 4Quest Clinical Res, San Francisco, CA, US; 5Ctr de Referencia e Treinamento DST/AIDS, Sao Paulo, Brazil; 6Private Practice, Los Angeles, CA, US; 7Tibotec BVBA, Mechelen, Belgium; and 8Tibotec, Inc, Yardley, PA, US
Background: New, potent, and tolerable
antiretrovirals are needed, particularly for treatment-experienced,
multidrug-resistant HIV-1 patients
Methods: DUET-1 is an ongoing
96-week randomized, double-blind phase III trial evaluating the efficacy and
safety of TMC125 200 mg vs placebo, both given twice daily. All patients
received a background regimen of darunavir/ritonavir (DRV/r),
investigator-selected NRTI and optional enfuvirtide (ENF). Patients had
documented NNRTI resistance and ³3 primary protease inhibitor (PI) mutations. The
primary efficacy endpoint for this week-48 analysis was the percentage of
patients with confirmed viral load <50 copies/mL. Safety was assessed
throughout the study.
Results: We included 612 patients
in the intent-to-treat population (62% CDC Category C,
median NNRTI mutations 2, 25% de novo ENF use) with a median baseline viral load 4.9 log10 copies/mL
and CD4 count 106 cells/mm3. Of
patients with viral load <50 copies/mL at week 24,
94% of patients maintained viral load <50 copies/mL
at week 48 with TMC125 + background regimen vs 89% with placebo + background
regimen. In addition, at week 48 the mean CD4 cell count was significantly
increased in the TMC125 vs the placebo group. As at week 24, safety assessments
at week 48 showed that the incidences of any adverse events (96% TMC125 vs 97%
placebo), serious adverse events (19% vs 25%), and grade-3 or -4 adverse events
(29% vs 36%) with TMC125 were similar to placebo. Most adverse events with
TMC125 were mild to moderate in severity and infrequently led to
discontinuation (6.6% vs 6.8%). Rash (any type) (22% vs 11%), diarrhea (14% vs
24%), and nausea (15% vs 15%) were the most common adverse events. Nervous
system (18% vs 21%) and psychiatric disorders (14% vs 18%) with TMC125 were
comparable to placebo.
Conclusions: TMC125 with a background regimen of
DRV/r plus optimized NRTI and optional ENF, provided durable and statistically
superior efficacy vs placebo over 48 weeks in treatment-experienced patients
with NNRTI-resistant virus. Except for rash, which was generally mild to
moderate, tolerability of TMC125 was similar to placebo.
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